Neurobiological correlates of alcohol intoxication and addiction were investigated in rats physically dependent upon ethanol. Correlative studies were conducted to characterize A) synaptosomal plasma membrane (SPM) composition, B) blood plasma cholesterol levels (BChL), and C) neuronal cell degeneration. A) Membrane composition. Membrane composition and fluid properties changed with the onset of the two phases of the ethanol withdrawal period. Increases in microviscosity, a decrease in the flow activation energy, marked increases in the molar ratios of cholesterol-to-phospholipid and cholesterol-to-protein suggest increased rigidity (organization) of the SPM. B) Elevation of blood cholesterol levels. During the induction period blood cholesterol levels increased from 50-70 mg/dl (days) 1) to 160 mg/dl on the withdrawal day (day 5). As the withdrawal syndrome evolved, there was a steady decline in the BChL, which returned to control values 7-10 days after withdrawal from ethanol. C) Neuronal cell degeneration. The onset of neuronal silver staining, an indicator of cell degeneration, was observed as early as the second day of the induction period. The argyrophilic cell bodies were seen for several days after the initiation of the withdrawal period. These investigations further characterize our rat model of physical dependence upon ethanol. These findings indicate that: 1) the fluid properties and chemical composition of SPM change in parallel with the onset and decay of neurological and behavioral signs and responses characteristic of the two phases of the withdrawal period, 2) the elevation of the cholesterol in the SPM is paralleled by a similar increase in the blood cholesterol levels, and 3) short term chronic ethanol intoxication results in degeneration of neuronal cells.